The proposed research is intended to assess the potential usefulness of several vasodilator agents in overcoming experimentally induced small intestinal ischemia and hypoxia, as well as exploring two biochemical mechanisms which may be involved in vasodilation in the mesenteric circulation. These proposed studies would constitute a systematic assessment of hemodynamic effects of dilator drugs on the vasculature of the gut. We would measure total blood flow to the small intestine of anesthetized dogs and monkeys and would also measure the pressure gradient across the gut, the arteriovenous oxygen content gradient, the distribution of radiolabelled microspheres, the clearance of 86Rb and the distribution of radiolabelled erythrocytes. From these measurements we would be able to determine vascular resistance, oxygen consumption and the density of perfused capillaries within the wall of the small intestine, as well as the fractional blood flow to the mucosa and the availability of oxygen in the villi and mucosa. These parameters would be determined with each dilator drug during direct infusion into the superior mesenetric artery. Examining this range of drug effects upon various components of the mesenteric circulation would permit discrimination between more favorable agents and less useful drugs. In addition, we would examine the effects of dilator agents and digitalis on the Na ion, K ion - ATPase, adenylate cyclase activities and cyclic AMP content of the mesenteric artery under both in vitro and in vivo conditions to determine early biochemical responses to the drugs. The latter studies would permit definition of vasodilation in molecular terms.